Mesoscopic models of neurotransmission as intermediates between disease simulators and tools for discovering design principles.

Two grand challenges have been declared as premier goals of computational systems biology. The first is the discovery of network motifs and design principles that help us understand and rationalize why biological systems are organized in the manner we encounter them rather than in a different fashion. The second goal is the development of computational models supporting the investigation of complex systems, in particular, as simulation platforms in personalized medicine and predictive health. Interestingly, most published systems models in biology contain between a handful and a few dozen variables. They are usually too complicated for systemic analyses of organizing principles, but they are at the same time too coarse to allow reliable simulations of diseases. While it may thus appear that the modeling efforts of the past have missed the declared targets of systems biology, we argue in this article that midsized mesoscopic models are excellent starting points for pursuing both goals in computational systems biology.

Prevalence and correlates of hepatitis C infection among users of North America's first medically supervised safer injection facility.

BACKGROUND: North America's first medically supervised safer injection facility (SIF) for illicit drug users was opened in Vancouver, Canada on 22 September 2003. We examined the prevalence and correlates of hepatitis C (HCV) infection among a representative cohort of SIF users. METHODS: Users of the Vancouver SIF were selected at random and asked to enrol in the Scientific Evaluation of Supervised Injecting (SEOSI) cohort. At baseline, venous blood samples were collected and an interviewer-administered questionnaire was performed. Participants who were HCV-positive were compared with HCV-negative subjects using bivariate and logistic regression analyses. RESULTS: Between 1 December 2003 and 30 July 2004, 691 participants were enrolled into the SEOSI cohort, among whom 605 (87.6%) were HCV-positive at baseline. Factors independently associated with HCV infection in logistic regression analyses included: involvement with the sex trade [adjusted odds ratio (AOR) 3.7, 95% confidence interval (CI) 2.1-6.1], history of borrowing syringes (AOR 1.8, 95%CI 1.1-2.9), and history of incarceration (AOR 2.6, 95%CI 1.5-4.4). Daily heroin use was protective against HCV infection (AOR 0.6, 95%CI 0.3-0.9). CONCLUSION: The SIF has attracted injection drug users with a high burden of HCV infection and a substantial proportion of uninfected individuals. Although cross-sectional, this study provides some insight into historical risks for HCV infection among this population, and prospective follow-up of this cohort will be useful to determine if use of the SIF is associated with reduced risk behaviour and HCV incidence.

[Separation of enantiomeric labetalol by reversed-phase high performance liquid chromatography].

A reversed-phase high performance liquid chromatographic method for the separation of labetalol enantiomers was developed. In the method, 2, 3, 4, 6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC) was chosen as the reagent for pre-column chiral derivatization of labetalol to give four diastereomeric thiourea derivatives. These derivatives were efficiently separated on a Nova-Pak C18 column using V(MeOH):V(0.01 mol.L-1(pH 7.00) H2PO4(-)-HPO(4)2- buffer) = 51:49 as the mobile phase and detected by UV detector at a wavelength of 250 nm or fluorescence detector at lambda ex = 340 nm and lambda em = 440 nm. The effects of the pH of mobile phase on the retention and fluorescence absorbance are also discussed.

Efficient visible femtosecond optical parametric generator and amplifier using tilted pulse-front pumping.

Using pulses with tilted pulse fronts to compensate for the group-velocity mismatch in three-wave interactions, we constructed an efficient 400-nm pumped femtosecond collinear typeI phase-matched beta -barium borate optical parametric generator and amplifier. The signal and idler outputs are tunable from 470nm to 2.7 microm and have pulse widths in the range of 100170fs at a 1-kHz repetition rate. A maximum output energy of 6.5 microJ and a total conversion efficiency of more than 15% were achieved.

Cloning of a third mammalian Na+-Ca2+ exchanger, NCX3.

NCX3 is the third isoform of a mammalian Na+-Ca2+ exchanger to be cloned. NCX3 was identified from rat brain cDNA by polymerase chain reaction (PCR) using degenerate primers derived from the sequences of two conserved regions of NCX1 and NCX2. The NCX3 PCR product was used to isolate two overlapping clones totalling 4.8 kilobases (kb) from a rat brain cDNA library. The overlapping clones were sequenced and joined at a unique Bsp106I restriction enzyme site to form a full-length cDNA clone. The NCX3 cDNA clone has an open reading frame of 2.8 kb encoding a protein of 927 amino acids. At the amino acid level, NCX3 shares 73% identity with NCX1 and 75% identity with NCX2 and is predicted to share the same membrane topology as NCX1 and NCX2. Following addition of a poly(A)+ tail to the NCX3 clone, exchanger activity could be expressed in Xenopus oocytes. NCX3 was also expressed in the mammalian BHK cell line. NCX3 transcripts are 6 kb in size and are highly restricted to brain and skeletal muscle. Linkage analysis in the mouse indicated that the NCX family of genes is dispersed, since the NCX1, NCX2, and NCX3 genes mapped to mouse chromosomes 17, 7, and 12, respectively.

[A comparison of incidence of dental caries among primary and middle school pupils in Shanghai at 1982 and 1990].

In 1982 and 1990, two epidemiological surveys of dental caries of primary and middle school in Shanghai were carried out, using similar standards and methods. A comparison of the results revealed that: the incidence of caries of milk teeth continued to stay at a high level; the incidence of caries of permanent teeth showed a marked reduction. There was no difference between the two sexes. The incidence of caries of permanent teeth of the urban pupils is higher than that of the rural ones. Conversely, the incidence of caries of milk teeth of the rural pupils is still higher than that of the urban ones.